Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Considering the good penetration of systemic high-dose ara-C (HDara-C) into the CNS, we used this approach for treating overt meningeal leukemia, either isolated or with concurrent extraneurologic disease, in 15 adults with high-risk acute lymphoblastic leukemia (ALL), one adult with lymphoid blast crisis of chronic granulocytic leukemia (LBC-CGL), and four adults with poor-prognosis non-Hodgkin's lymphoma (NHL). Treatment consisted of ara-C, 3 g/m2 every 12 hours by three-hour infusion for eight doses followed by a second course of four doses on day 21. Remitters received consolidation with monthly courses of HDara-C for four doses. Additional systemic multi-drug reinduction therapy and direct CNS treatment with intrathecal methotrexate (IT MTX) and cranial irradiation (CRT) was administered to the three remitters last treated. Thirteen of 20 patients (65%) achieved complete remission (CR): seven of seven patients with isolated meningeal leukemia and six of 13 patients with concurrent CNS and bone marrow disease. Of the remaining seven patients, five had a complete CSF clearing with persistent marrow disease. In all cases there was prompt resolution of neurologic signs and symptoms. The median duration of CR was 5 months (range 2 to 8 months). The most significant toxicity seen was myelosuppression, which was predictable and manageable. Nonhematologic toxicity was generally acceptable and included moderate nausea and vomiting, diarrhea, drug fever, transient liver dysfunction, and dermatitis. No cases of CNS toxicity occurred. There were no treatment-related deaths. Disease-free survival was limited by marrow relapse, either isolated or with concurrent CNS disease. No instances of isolated meningeal relapse occurred. These results obtained in a poor-risk subset of patients indicate that HDara-C is an effective treatment for the induction of remission in ALL and NHL with meningeal leukemia. Therefore, HDara-C should be considered for inclusion in multiagent consolidation programs for patients at high risk for CNS disease.
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PMID:Systemic high-dose ara-C for the treatment of meningeal leukemia in adult acute lymphoblastic leukemia and non-Hodgkin's lymphoma. 346 Nov 34

Nine patients with onco-hematological malignancies with a poor prognosis due to high risk of relapse received immunotherapy with interleukin-2 (IL-2) and interferon (IFN(alpha 2b)) s.c. as maintenance therapy after receiving autologous bone marrow or peripheral blood stem cell transplantation (ABMT/PBSCT). All the patients were considered at very high risk of relapse. We attempted to assess the efficiency, toxicity and clinical effects of these cytokines in these patients. Five patients were treated with high-dose of IL-2 and the other four patients with escalating doses every month. Side-effects in the first group of patients consisted of fever, chills, weakness, nausea, anorexia, loss of weight and local dermatitis in the injection site. Toxicity on the WHO scale was grade II in three patients and grade IV in the other two patients. In the second group of patients, the same clinical signs of toxicity appeared, but these were grade I on the WHO scale in all patients. None of the patients had infections or died in relation to administration of IL-2. Four patients died of relapse or progression of their hematological malignancies. The other five patients are alive, one in chronic phase of CML and the other four patients are in complete remission of their malignancies.
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PMID:Treatment with interleukin-2 (IL-2) and interferon (IFN(alpha 2b)) after autologous bone marrow or peripheral blood stem cell transplantation in onco-hematological malignancies with a high risk of relapse. 1019 3

A 29-year-old man was referred to our hospital with leukocytosis on March 7th, 2002. The white blood cell count was 132.9 x 10(3)/microliter with 42.0% blast cells. We diagnosed Philadelphia chromosome-positive chronic myelogenous leukemia (CML) in a blast crisis and started imatinib mesylate therapy at a dose of 800 mg/day on March 9th, 2002. The patient's peripheral blood blasts had disappeared by March 22nd, 2002, and the percentage of blasts in the bone marrow was 0.6% on May 2nd, 2002. The patient achieved a complete cytogenetic response on May 13th, 2002, and underwent allogeneic peripheral blood stem cell transplantation from his HLA-identical sibling donor on May 30th, 2002. Although adverse reactions such as grade 3/4 of hematological events (leukopenia, anemia, thrombocytopenia and neutropenia) and grade 1/2 of non-hematological events (hyperbilirubinemia, dermatitis and edema) were observed, these adverse reactions were clinically managed. This case suggested the usefulness of imatinib mesylate in the management of the CML-associated blast crisis.
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PMID:[Successful induction of complete cytogenetic response with high-dose imatinib mesylate and subsequent allogeneic stem cell transplantation for CML blastic crisis]. 1288 17

Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder characterized by the balanced reciprocal translocation t (9:22). The resulting fusion gene, the BCR-ABL, is responsible for oncogenesis. Imatinib mesylate is a novel molecule, which inhibits the protein product of this fusion gene and hence has been used in the treatment of CML. The present study evaluates 174 patients with CML treated with imatinib mesylate. Of these 174 patients, 97 were in chronic phase, 47 in accelerated phase and 30 patients had blast crisis. Patients in chronic phase received imatinib mesylate in the dose of 400-mg daily, while those in accelerated phase and blast crisis received 600 to 800 mg daily. Of the 97 patients with chronic phase, 49 patients (50.5%) achieved a major (major + complete) cytogenetic response. Of the 47 patients in accelerated phase, 10 patients (21.3%) achieved a major cytogenetic response and in 30 patients with blast crisis, 7 (23.3%) achieved a major cytogenetic response. Dermatitis, mucositis, neutropenia and thrombocytopenia were some of the major toxicities. Of interest, 121 of the 174 patients (69.5%) developed generalized hypopigmentation. We conclude that imatinib mesylate is a safe and effective first-line therapy for chronic myeloid leukemia.
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PMID:Imatinib mesylate in chronic myeloid leukemia: a prospective, single arm, non-randomized study. 1598 13

Progesterone induced dermatitis is a rare disorder. It typically occurs in females due to an autoimmune phenomenon to endogenous progesterone production, but can also be caused by exogenous intake of a synthetic progestin. Here in, we present a case of autoimmune progesterone anaphylaxis (AIPA) observed in an adolescent female. The patient is an 18-year-old Caucasian female with no significant past medical history and no prior exogenous hormone use, who presented to her primary care physician complaining of cyclic skin eruptions with dyspnea, cough and respiratory distress. She noted that her symptoms occurred monthly, just prior to her menses. An intradermal skin test using 0.1 cml of progesterone was performed. The patient developed a 15 mm wheal after 15 minutes, confirming the diagnosis of AIPA. The patient was started on a continuous regimen of an oral conjugated estrogen (0.625 mg). The skin eruptions and respiratory symptoms have not returned since the initiation of this therapy. Autoimmune progesterone dermatitis manifests via the occurrence of cyclic skin eruptions. Women with the disorder commonly present with dermatologic lesions in the luteal phase of the menstrual cycle, if there are any other organ involvement in addition to skin (e.g. lung, GI) the reaction should be called as autoimmune progesterone anaphylaxis. Diagnosis of AIPA is confirmed by performing a skin allergen test using progesterone.
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PMID:Autoimmune progesterone anaphylaxis. 1756 11

We describe a 64-year-old man with past chronic myeloid leukemia. Palisading neutrophilic granulomatous dermatitis of the hands was diagnosed and related to recent allopurinol intake. Allopurinol is known to rarely cause granulomatous reactions, but this appears to be the first case of palisading neutrophilic granulomatous dermatitis induction. Possible mechanisms include immune complex deposition, an immune response directed against the metabolites of allopurinol, or allopurinol hypersensitivity exclusively localized to the skin.
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PMID:Allopurinol-induced palisaded neutrophilic and granulomatous dermatitis. 2225 Aug 12

Imatinib mesylate is a receptor kinase inhibitor approved by the Food and Drug Administration for the treatment of malignant metastatic and/or unresectable gastrointestinal stromal tumors and chronic myelogenous leukemia. Although imatinib is generally well tolerated, certain adverse drug reactions are common. These include gastrointestinal side-effects such as diarrhea, nausea and vomiting, as well as hematological side-effects and other miscellaneous side-effects such as fatigue, edema, dermatitis and dyspnea. We present a previously unreported adverse effect of imatinib, gastric antral vascular ectasia, in a 74-year-old woman with gastrointestinal stromal tumor in remission treated with adjuvant imatinib. Endoscopy performed prior to starting imatinib showed normal gastric mucosa, but 8 months after starting imatinib showed diffuse gastric inflammation. Repeat endoscopy 1 month after discontinuing imatinib showed significant improvement in gastric inflammation.
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PMID:Gastric antral vascular ectasia in a patient with GIST after treatment with imatinib: case report and literature review. 2242 98

Neutrophilic dermatosis (ND) confined to postmastectomy lymphedema, localized Sweet syndrome, is a newly recognized disease. In this study, the authors describe a 44-year-old obese woman with chronic myelogenous leukemia in molecular remission on dasatinib therapy, who presented with a painful urticarial eruption limited to lipo-lymphedematous skin and accompanied by malaise, episodic fever, diarrhea, neutrophilia, and leukocytosis. Initially transient and migratory, the rash became fixed, papular, and vesicular and showed minimal response to corticosteroids. Biopsy demonstrated sparse perivascular and interstitial dermal neutrophilic infiltrates, without vasculitis or significant dermal edema. Aggregates of neutrophils were found within and surrounding lymphangiectases. Biopsy of a new onset papule 3 weeks later demonstrated papillary dermal edema, denser neutrophilic infiltrate, and vasculitis-like changes. These 2 histopathologic patterns of ND, early and late, resemble neutrophilic urticarial dermatitis (also known as neutrophilic dermatitis with systemic inflammation) and Sweet syndrome, respectively. Extensive workup did not reveal evidence of relapsed chronic myelogenous leukemia, infection, or a coexisting systemic inflammatory disease. Dasatinib was discontinued and the eruption gradually resolved over 2.5 months. Still in molecular remission (no detectable BCR-ABL gene fusion), dasatinib therapy was recommenced at 3-month follow-up. After 10 months, she complains of malaise and arthralgia, but no cutaneous symptoms. The evolution and slow resolution of this ND in lipo-lymphedematous skin implicate poor lymphatic clearance of factors, antigenic and/or toxic, involved in the pathogenesis of ND.
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PMID:Neutrophilic Dermatosis Limited to Lipo-Lymphedematous Skin in a Morbidly Obese Woman on Dasatinib Therapy. 2682 66

The co-occurrence of different types of hemo-lymphopoietic malignancies within a family provides clues about the pattern of inheritance and common environmental risk factors. A family presented with developing hemo-lymphopoietic cancers in three female first-degree relatives: a mother and her daughters. Case 1 was diagnosed with Walden Strom's macroglobulinemia at age 57. Case 2 and 3 presented with chronic myelogenous leukemia at age 32 and diffuse large B-cell lymphoma at age 28, respectively. There were not any significant common environmental risk factors in this family, but all three cases suffered from skin dermatitis and one of them, who suffered from chronic myelogenous leukemia, was diagnosed with morphea. This family had a sedentary and stressful lifestyle. Genetic is the foundation of some familial aggregation of cancers. Common lifestyle habits and environmental etiologies are important. Morphea as an autoimmune disease could have the essential role in developing hematolymphoid malignancies.
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PMID:Hemo-Lymphopoietic Malignancies Surround the Women of the Family: A Case Report and Literature Review. 3023 69